A group of arylalkyl isothiocyanates were tested for their
abilities toinhibit tumorigenicity and DNA methylation induced by
theesophageal-specific carcinogen,<it>N-nitrosomethylbenzylamine
(NMBA) in the F344 ratesophagus. Phenylpropyl isothiocyanate (PPITC)
was more potent than eitherphenylethyl isothiocyanate (PEITC) or
benzyl isothiocyanate (BITC).Phenylbutyl isothiocyanate (PBITC),
however, had a lesser inhibitory effecton esophageal tumorigenesis,
and phenylhexyl isothiocyanate (PHITC)actually enhanced esophageal
tumorigenesis. Thus, the two- and three-carbonisothiocyanates were
more effective inhibitors of NMBA-esophagealcarcinogenesis than the
longer chain isothiocyanates. The effects of theisothiocyanates on
tumorigenesis were well correlated as to their effectson DNA adduct
formation. The most likely mechanism of inhibition oftumorigenesis
by these isothiocyanates is via inhibition of the cytochromeP450
enzymes responsible for the metabolic activation of NMBA in ratesophagus.
A freeze-dried strawberry preparation was also evaluated for itsability
to inhibit NMBA-esophageal tumorigenesis. It proved to be aneffective
inhibitor, although not as potent as either PEITC or PPITC. Theinhibitory
effect of the berries could not be attributed solely to thecontent
of the chemopreventive agent, ellagic acid, in theberries.